Does a patient with gastroesophageal reflux disease (GERD) experience increased inflammation and coughing at night due to lower cortisol levels?

Nighttime Coughing in GERD: The Cortisol Question

The increased coughing and inflammation at night in GERD patients is NOT primarily caused by lower cortisol levels—instead, it results from the supine position facilitating acid reflux and microaspiration, combined with the fact that objective cough monitoring shows cough is actually suppressed during true sleep. 1

Why Nighttime Symptoms Occur in GERD

Primary Mechanism: Positional Reflux

• The supine position at night facilitates acid reflux into the esophagus and potential microaspiration into the airways, making GERD particularly problematic during nighttime hours. 1
• Nocturnal symptoms are characteristic of GERD: cough exacerbated by meals, positional worsening when lying down, and improvement with head-of-bed elevation. 1, 2
• GERD can stimulate cough through three distinct pathways: direct laryngeal irritation without aspiration, microaspiration/macroaspiration of gastric contents into airways, and an esophageal-bronchial reflex where refluxate in the distal esophagus alone triggers neural pathways. 2

The Sleep-Cough Paradox

• Objective cough counts demonstrate that spontaneous cough is actually suppressed during true sleep, meaning most "nocturnal" coughing occurs during brief awakenings rather than during sleep itself. 1
• This finding contradicts the assumption that nocturnal cough equals poorly controlled inflammation—the timing relates more to position and arousal states than inflammatory cycles. 1

The Cortisol-Inflammation Relationship: Not What You'd Expect

Cortisol's Complex Role

• Recent research reveals that cortisol exerts bi-phasic regulation of inflammation: it can be both pro-inflammatory and anti-inflammatory depending on concentration, timing, and context. 3
• Baseline diurnal cortisol concentrations do not exert an anti-inflammatory effect, challenging the linear dose-response assumption. 3
• Cortisol can actually enhance proinflammatory responses when combined with immune-activating cytokines like interferon-γ, increasing inflammatory mediator release by more than 4-fold in some contexts. 4

Why This Doesn't Explain GERD Cough

• While cortisol levels do follow a diurnal pattern (lowest in early morning), there is no evidence linking these fluctuations to GERD-related cough severity. 5
• Children with GERD show elevated cortisol levels that intensify catabolic processes and disturb the balance of aggressive-protective factors in the gastroduodenal zone, but this represents chronic dysregulation rather than diurnal variation. 5
• The definitive diagnosis of cough due to GERD requires that cough nearly or completely disappear with antireflux treatment, not with cortisol manipulation. 6

Clinical Implications and Management

Diagnostic Approach

• Up to 75% of patients with GERD-induced cough have no typical GI symptoms like heartburn ("silent GERD"), making the diagnosis easily missed. 1, 7, 2
• Do not rule out GERD based on absence of heartburn—the majority of reflux-related cough patients have no GI symptoms. 1, 7
• The 24-hour esophageal pH-monitoring test is the most sensitive and specific test, but results should be interpreted as normal only when conventional indices for acid reflux are within normal range AND no reflux-induced coughs appear during monitoring. 6

Treatment Strategy

• Initiate intensive antireflux therapy including proton pump inhibitor (PPI) twice daily for a minimum of 8-12 weeks—this is much longer than typical GERD treatment. 1, 2
• Positional therapy is essential: elevate the head of bed and avoid meals within 3 hours of bedtime to address the mechanical component of nighttime reflux. 7, 2
• If empiric PPI therapy fails after 3 months of intensive treatment, perform 24-hour esophageal pH monitoring to confirm diagnosis and assess adequacy of acid suppression. 1
• Laparoscopic antireflux surgery shows 85-86% improvement rates in chronic cough at 6-12 months for patients who fail maximal medical therapy. 1, 2

Critical Pitfalls to Avoid

• Do not use short-term PPI trials (1-4 weeks) to diagnose GERD-related cough—these are inadequate for extraesophageal symptoms and require 8-12 weeks minimum. 1
• Do not assume nocturnal cough equals poorly controlled asthma—cough is suppressed during true sleep, and timing relates to position and brief awakenings. 1
• Do not stop treatment prematurely—there can be a delay of 2 to 3 months in improvement with therapy that will eventually eliminate the cough. 6
• Do not assume GERD has been ruled out simply because there is a history of antireflux surgery—GERD can persist post-operatively. 6